The periodontal diseases are the most common cause of tooth loss. They are becoming relatively more important in dentistry as dental caries is brought under control. These diseases are caused by the interaction of bacteria and their products with host defense mechanisms resulting in damage to the connective tissue and bone. Similar tissue alterations are an important component of many other chronic diseases as well. Some of the mechanisms underlying these alterations remain to be elucidated, especially the role resident fibroblasts play and alterations in the non-collagenous matrix constitutents. We propose to continue our analysis of normal and diseased connective tissue matrix components, using ginggival tissue as a model, and to learn more about the role fibroblasts play in normal and disease processes. We will isolate from dog gingiva and characterize a family of non-collagenous proteins which comprise a large portion of the matrix. At least three of the eight components will be purified to homogeneity and studied with regard to chemoattractant activity for fibroblasts and leukocytes, role in cell attachment, and interactions with other structural macromolecules, especially the collagens. Fibroblasts play a key role in production and maintenance of the normal matrix components and in pathologic processes. Their activities are exquisitely regulated by interactions with ligands present in the fluids which bathe them. We have selected two ligands considered to be important in in vivo regulation, to study their influence on fibroblasts and their collagen production. We will analyze the mechanisms by which platelet-derived growth factor and substances released by activated lymphocytes affect collagent production by evaluating their effect on membrane transport, intracellular and extracellular degradation and mRNA levels. In addition, we will define the role of the C1 component of the complement and its subcomponents, especially C1q and complexes containing C1q, in regulating fibroblast growth and synthesis activities.